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Sphingomyelin synthase 1 is essential for male fertility in mice.
PLoS ONE 11:e0164298 (2016)
Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. Lipid profiling revealed a reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids in the testes of mutants. Multi-Spectral Optoacoustic Tomography indicated blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminished germ cell sloughing from the seminiferous epithelium and restored spermatogenesis and fertility in 50% of previously infertile mutants. Our findings indicate that SMS1 has a wider than anticipated role in testis polyunsaturated fatty acid homeostasis and for male fertility.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Polyunsaturated Fatty-acids; Double-strand Breaks; Long-chain; Germ-cells; Mammalian Spermatogenesis; Chromosome Inactivation; Lysine-9 Methylation; Mass-spectrometry; Deficient Mice; Sertoli-cells
ISSN (print) / ISBN
1932-6203
Journal
PLoS ONE
Quellenangaben
Volume: 11,
Issue: 10,
Article Number: e0164298
Publisher
Public Library of Science (PLoS)
Publishing Place
Lawrence, Kan.
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Peer reviewed